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Нейтрофильная активация и повторное расширение CAR-T, лежащее в основе синдрома высвобождения цитокина, во время цилакабтагенской автолексельной терапии в множестве миеломы.

Синдром цитокина (CRS) является наиболее распространенным осложнением химерика антигенного рецептора, перенаправления Т клеток (CAR-T). Существенно улучшено регулирование токсичности CAR-T, однако ДУС по-прежнему является одной из главных проблем в области безопасности. Здесь мы следим уровням сыворотки цитокина и циркулируем транскриптомы иммунных клеток в продольном направлении. 26 для понимания иммунологической кинетики CRS. Мы видим, что, хотя T лимфоциты и моноциты/макропаты являются основным общим источником цитокина в виде ДУС, нейтрофильная активация достигла пиков ранее, до появления

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… All the data were collected using an LSRII flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA) and were analyzed with FlowJo software V10 (TreeStar, Ashland, OR, USA). Gating strategy can be found in Supplementary Fig. 11 . …

Current drugs for HIV-1: from challenges to potential in HIV/AIDS.

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (

The Clinical Relevance of Selected Cytokines in Newly Diagnosed Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of

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… We also utilized the BD CBA Human IL-6 and IL-8 Enhanced Sensitivity Flex Set in conjunction with a BD CBA Human Enhanced Sensitivity Master Buffer Kit, a BD FACSCanto™ II flow cytometer, and FCAP Array™ Software version 3.0 (Becton Dickinson, Franklin Lakes, NJ, USA). …

Enhancement of Neuroblastoma NK-Cell-Mediated Lysis through NF-kB p65 Subunit-Induced Expression of FAS and PVR, the Loss of Which Is Associated with Poor Patient Outcome.

High-risk neuroblastoma (NB) is a rare childhood cancer whose aggressiveness is due to a variety of chromosomal genetic aberrations, including those conferring immune evasion. Indeed, NB cells adopt several molecular strategies to evade recognition by the immune system, including the downregulation of ligands for NK-cell-activating receptors. To date, while molecular strategies aimed at enhancing the expression of ligands for NKG2D- and DNAM-1-activating receptors have been explored, no evidence has been reported on the immunomodulatory mechanisms acting on the expression of death receptors su

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… For the blocking experiments, NK cells were pretreated for 20 min with 25 μg/mL of neutralizing anti-DNAM-1 (DX11, BD-Parmingen, Franklin Lakes, NJ, USA) or anti-FasL (NOK-1, Biolegend) before co-culture with target cells. …

Relative value assessment: characterizing the benefit of oncology therapies through diverse survival metrics from a US perspective.

ObjectivesThe introduction of innovative, high-cost oncology treatments, coupled with mounting budgetary pressures, necessitates value trade-offs across cancer types. Defining value is critical to informing decision-making. A cost-value analysis tool was used to assess relative clinical value from a US perspective using multiple outcome metrics for a variety of metastatic cancers.MethodsLiterature published (January 1, 2000-August 31, 2016) was reviewed to identify outcome metrics for approved treatments for metastatic cancers. Data were extracted or derived for median and mean overall surviva

NTP Toxicology and Carcinogenesis Studies of EMODIN (CAS NO. 518-82-1) Feed Studies in F344/N Rats and B6C3F1 Mice.

Emodin is a naturally occurring anthraquinone present in the roots and bark of numerous plants of the genus Rhamnus. Extracts from the roots, bark, and/or dried leaves of buckthorn, senna, cascara, aloe, frangula, and rhubarb have been used as laxatives since ancient times and currently are widely used in the preparation of herbal laxative preparations. Anthraquinone glycosides are poorly absorbed from the gastrointestinal tract but are cleaved by gut bacteria to produce aglycones (such as emodin) that are more readily absorbed and are responsible for the purgative properties of these preparat

Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

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Interpreting Randomized Controlled Trials.

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial's sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and tru

IL-22 способствует возникновению хронической гаммагерпесвирусной инфекции, поддерживая реакцию микробного центра.

Гаммагерпесвирусы, включая вирус Эпштейн-Барр (EBV) и герпесвирус, связанный с Карпози (KSHV), создают скрытые инфекции на протяжении всей жизни, которые способствуют множественным заболеваниям раком и множественным склерозом. Эти вирусы колонизируют наивные клетки B и приводят в действие мощный, поликлонный герминальный центр, чтобы расширить латентный вирусный резервуар и установить пожизненную инфекцию в клетках памяти B. Несмотря на клиническое бремя этих вирусов, факторы, способствующие хронической инфекции, по-прежнему плохо определены. " Interleukin-22 " (IL-22) является крити

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… Mice were bled before euthanasia via submandibular vein sampling, and the serum was collected using BD Microtainer blood collection tubes (Becton, Dickinson and Company, Franklin Lakes, NJ). …

Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function.

Multiple myeloma is a plasma cell malignancy with a poor prognosis despite the recent development of new therapeutic options. Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma cells and may be involved in the acquisition of resistance to conventional anti-proteasome treatments. In addition to displaying a deacetylase catalytic activity, HDAC6 plays an essential role in the regulation of autophagy and cell death by recognizing ubiquitinated motifs from misfolded proteins through its C-terminal ZnF-UBP binding domain. These defective proteins are sent to the aggresome to facilit

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… Cells were then washed twice with PBS and incubated with propidium iodide staining solution (2.5 μg/mL PI (BD Biosciences, Franklin Lakes, NJ, USA), 100 µg/mL RNAse A (Promega)) for 2 h at RT. …

Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

BackgroundLoss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor

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… Blood was stored in heparinized tubes (BD Microtainer ® PSI Tubes with Lithium Heparin (#365985; BD Biosciences, Franklin Lakes, NJ, USA), and plasma was extracted from blood by centrifugation at 5000 g for 5 min at 4 °C. …

Impact of Glucocorticoid Use in Oncology in the Immunotherapy Era.

Thanks to their anti-inflammatory, anti-oedema, and anti-allergy properties, glucocorticoids are among the most widely prescribed drugs in patients with cancer. The indications for glucocorticoid use are very wide and varied in the context of cancer and include the symptomatic management of cancer-related symptoms (compression, pain, oedema, altered general state) but also prevention or treatment of common side effects of anti-cancer therapies (nausea, allergies, etc.) or immune-related adverse events (irAE). In this review, we first give an overview of the different clinical situations where

An Individualized Exercise Intervention for People with Multiple Myeloma-Study Protocol of a Randomized Waitlist-Controlled Trial.

People with multiple myeloma (MM) are second only to people with lung cancer for the poorest reported health-related quality of life (HRQoL) of all cancer types. Whether exercise can improve HRQoL in MM, where bone pain and lesions are common, requires investigation. This trial aims to evaluate the efficacy of an exercise intervention compared with control on HRQoL in people with MM. Following baseline testing, people with MM (n = 60) will be randomized to an exercise (EX) or waitlist control (WT) group. EX will complete 12-weeks of supervised (24 sessions) and unsupervised (12 sessions) indiv

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… Supervised exercise sessions will be offered at multiple locations across southeast Queensland, Australia: North Lakes Health Precinct, Greenslopes Private Hospital, Princess Alexandra Hospital, Royal Brisbane and Women’s Hospitals Hospital, and The University of Queensland. …

T-Cell Acute Lymphoblastic Leukemia-Current Concepts in Molecular Biology and Management.

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are

A new era of natural killer cell immunotherapy in tumor treatment: latest advances and cutting-edge perspectives from basic research to clinical practice.

As early as 1863, Virchow observed that cancer often arises at sites of chronic inflammation. Modern epidemiological and clinical studies have confirmed the link between inflammation and cancer. Natural Killer (NK) cells actively participate in and regulate inflammatory processes; however, they are not strictly classified as classic 'inflammatory cells' in cellular taxonomy. NK cells rapidly identify and eliminate malignantly transformed cells in a non-major histocompatibility complex (MHC)-restricted manner, a characteristic that distinguishes them from other immune cells. Furthermore, their

Chimeric antigen receptor therapy for hematological malignancies: a pediatric perspective from leukapheresis to infusion.

Immunotherapy, particularly chimeric antigen receptor T cells (CAR T)s, has changed the landscape of B-cell malignancy treatment and represents a promising approach to cancer therapy. The use of CAR T-based therapy in pediatric patients presents several critical issues such as the quality of the leukapheresis process and the treatment-related toxicity. Nevertheless, the experience with anti-CD19 CAR Ts in treating pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) demonstrated its feasibility and efficacy with a complete response rate greater than 80%. Although CAR T therapy is

CT-based finite element simulating spatial bone damage accumulation predicts metastatic human vertebrae strength and stiffness.

Introduction: Pathologic vertebral fractures are devastating for patients with spinal metastases. However, the mechanical process underlying these fractures is poorly understood, limiting physician's ability to predict which vertebral bodies will fail. Method: Here, we show the development of a damage-based finite element framework producing highly reliable pathologic vertebral strength and stiffness predictions from X-Ray computed tomography (CT) data. We evaluated the performance of specimen-specific material calibration vs. global material calibration across osteosclerotic, osteolytic, and

Mucositis and Infection in Hematology Patients.

Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advanc

17th Конгресс ЕВНОС: Милан, Италия, 4–6 Июнь, 2026 года

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Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec